Delayed implantation and seasonal breeding

建议继续进行一项积极而成功的研究计划，以确定一种称为专性胚胎滞育(又名延迟着床)的生殖现象的特征和调节。当哺乳动物胚胎在胚泡阶段经历发育停滞时，就会发生滞育，随后被重新激活并植入以继续怀孕。这是一种进化策略，将交配从怀孕中分离出来，允许在最适合生存的季节分娩。滞育是包括黄鼠狼、熊和海豹在内的几个食肉动物家族的受孕过程。从春季繁殖食肉动物的几周持续到秋季交配的物种的几个月。该建议基于这样的假设，即胚胎滞育由子宫分泌的因素调节，而胚胎植入是由激活的胚胎启动和协调的。总的目标是确定胚胎滞育的发育停滞的细胞机制，并探索胚胎-子宫对话重新激活胚胎并诱导着床进入子宫。所使用的模型是牧场水貂。第一个具体目标是利用我们最近的基因发现研究结果来确定子宫和胚胎调节胚胎进入和退出滞育的机制。通过探索细胞信号和细胞周期调控基因的表达，在体外记录的桑椹胚期和进入滞育阶段的胚胎将被收集，在体内收集的胚胎将从滞育中退出。将测试子宫分泌因子的表达模式以及它们在体外激活胚胎的能力。第二个特定的目标是研究滋养细胞作为局部着床过程的调节器，以及子宫内膜的侵袭。它将通过检查侵袭性成分合体滋养细胞的形成和调节，以及研究子宫重塑的形态和基因表达事件来解决。这些新的实验和方法将获得对滞育和着床的新见解，以及对理解其他哺乳动物的胎盘形成和胚胎丧失具有重要意义的信息。

Continuation of an active and successful research program to determine characteristics and regulation of a reproductive phenomenon known as obligate embryonic diapause (aka delayed implantation) is proposed. Diapause occurs when mammalian embryos undergo developmental arrest at the blastocyst stage, to be later reactivated and implanted for continuation of pregnancy. It is an evolutionary strategy that uncouples mating from gestation, allowing parturition at the optimal season for survival. Diapause is in the gestational program of several carnivore families including the weasels, bears and seals. It persists from a few weeks in spring breeding carnivores to several months in species that mate in the fall. The proposal is based on the hypothesis that embryonic diapause is regulated by factors secreted by the uterus, while embryo implantation is initiated and orchestrated by the activated embryo. The overall objective is to determine the cellular mechanisms of the developmental arrest in embryonic diapause and to explore the embryo-uterine dialog that reactivates the embryo and induces implantation into the uterus. The model employed is the ranch mink. The first specific objective is to exploit results of our recent gene discovery investigation to determine mechanisms by which the uterus and embryo regulate entry and exit of the embryo from diapause. Embryos will be collected at the morula stage and entry into diapause chronicled in vitro, as will exit from diapause in embryos collected in vivo, by probing for expression of cell signaling and cell cycle regulatory genes. The pattern of expression of factors secreted by the uterus and their capacity to reactivate embryos in vitro will be tested. The second specific objective is to investigate trophoblast as a regulator of local processes of implantation, and endometrial invasion. It will be addressed by examination of formation and regulation of the invasive component, the syncytial trophoblast and by investigation of morphological and gene expression events of uterine remodeling. New insight into diapause and implantation and information significant to understanding placental formation and embryo loss in other mammals will be gained from these novel experiments and approaches.